2-mercaptomethylene-tetrahydronaphthalene and indane-2-carboxamide derivatives as enkephalinase inhibitors

Abstract

The present invention relates to novel 2-mercaptomethylene-tetrahydronaphthalene derivatives which are useful as enkephalinase inhibitors.

What is claimed is: 
     
       1. A compound of the formula ##STR29## wherein n is an integer 2, Z is the radical --C(O)OR, or a phenyl group unsubstituted or substituted with from 1 to 3 substituents selected from the group consisting of OH, C 1  -C 4  alkoxy, and methylenedioxy,   R is H, C 1  -C 4  alkyl, or benzyl,   R 1  is H or --C(O)--A, wherein A is C 1  -C 4  alkyl, or phenyl, and   B is a radical of the formula ##STR30## wherein m is an integer 0 to 5, and   R 2  is H, C 1  -C 4  alkyl, --CH 2  --OH, --CH(OH)--CH 3 , --CH 2  CH 2  SCH 3 , phenylmethyl, 4-hydroxy-phenylmethyl or OH, with the proviso that R 2  cannot be OH when m is 0.   
     
     
       2. A compound according to claim 1 wherein n is 1. 
     
     
       3. A compound according to claim 1 wherein n is 2. 
     
     
       4. A compound according to claim 3 wherein B is ##STR31## 
     
     
       5. A compound according to claim 4 wherein m is 0. 
     
     
       6. A compound according to claim 4 wherein m is 1. 
     
     
       7. A method of inhibiting enkephalinase in a patient in need thereof comprising administering to said patient an effective enkephalinase inhibitory amount of a compound of claim 1. 
     
     
       8. A method according to claim 7 wherein the patient is in need of an endorphin- or enkephalin-mediated analgesic effect. 
     
     
       9. A method according to claim 7 wherein the patient is in need of an ANP-mediated hypotensive effect. 
     
     
       10. A method according to claim 7 wherein the patient is in need of an ANP-mediated diuretic effect. 
     
     
       11. A method according to claim 7 wherein the patient is in need of an antidiarrheal effect. 
     
     
       12. A method according to claim 7 wherein the patient is suffering from Alzheimer's Disease. 
     
     
       13. A composition comprising an assayable amount of a compound of claim 1 in admixture or otherwise in association with an inert carrier. 
     
     
       14. A pharmaceutical composition comprising an effective immunosuppressive amount of a compound of claim 1 in admixture or otherwise in association with one or more pharmaceutically acceptable carriers or excipients. 
     
     
       15. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercarptomethyl)-2-naphthalenyl]carbonyl]-glycine. 
     
     
       16. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercarptomethyl)-2-naphthalenyl]carbonyl]-L-alanine. 
     
     
       17. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercarptomethyl)-2-naphthalenyl]carbonyl]-L-valine. 
     
     
       18. A compound of claim 1 wherein the compound is 4[[[1,2,3,4-Tetrahydro-2-(mercarptomethyl)-2-naphthalenyl]carbonyl]amino]-cis-cyclohexanecarboxylic acid. 
     
     
       19. A compound of claim 1 wherein the compound is N-[[1,2,3,4-tetrahydro-2-(mercarptomethyl)-2-naphthalenyl]carbonyl]-β-alanine. 
     
     
       20. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercapto)methyl-2-naphthalenyl]carbonyl]-3,4-dihydroxybenzylamide. 
     
     
       21. A compound of claim 1 wherein the compound is N-[[1,2,3,4-tetrahydro-2-[(acetylthio)methyl]-2-naphthalenyl]carbonyl]-3,4-dihydroxybenzylamide. 
     
     
       22. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercaptomethyl)-2-naphthalenyl]carbonyl]-isoserine. 
     
     
       23. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-(mercaptomethyl)-2-naphthalenyl]carbonyl]-isoserine, benzyl ester. 
     
     
       24. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-[(acetylthio)methyl]-2-naphthalenyl]carbonyl]-isoserine. 
     
     
       25. A compound of claim 1 wherein the compound is N-[[1,2,3,4-Tetrahydro-2-[(acetylthio)methyl]-2-naphthalenyl]carbonyl]-isoserine, benzyl ester.